Background: Brain abscesses and ischaemic strokes complicate pulmonary arteriovenous malformations (PAVMs). At risk individuals are poorly recognised. Stroke/ abscess risk factors have not been defined. Methods: A cohort study of 323 consecutive individuals with PAVMs (n = 219) and/or the commonly associated condition hereditary haemorrhagic telangiectasia (HHT, n = 305) was performed. Most of the 201 individuals with PAVMs and HHT had no respiratory symptoms, and were unaware they had HHT. Anderson-Gill models assessed constant and time dependent potential predictive variables for stroke/abscess, and rate reduction by PAVM embolisation. Results: 57 individuals with PAVMs and HHT experienced brain abscess or ischaemic stroke, usually prior to the diagnosis of underlying PAVMs/HHT. The primary determinants of stroke and abscess risks were unrelated to severity of PAVMs. Males had higher brain abscess rates (hazard ratio 3.61 (95% CI 1.58, 8.25), p = 0.0024); interventional histories and bacteriological isolates suggested dental sources. Once adjusted for gender, there was a marginal association between brain abscess and low oxygen saturation. For ischaemic stroke, there was no association with any marker of PAVM severity, or with conventional neurovascular risk factors. Surprisingly, low mean pulmonary artery pressure was strongly associated with ischaemic stroke (hazard ratio 0.89 (95% CI 0.83, 0.95) per mm Hg increase; p = 6.2610 25 ). PAVM embolisation significantly reduced ischaemic stroke rate (p = 0.028); no strokes/abscesses occurred following obliteration of all angiographically visible PAVMs. The mean PAVM diagnosis-treatment interval was longer, however, when neurological risks were unrecognised. Conclusions: Ischaemic strokes and brain abscesses occur commonly in undiagnosed HHT patients with PAVMs. Risk reduction could be improved.Pulmonary arteriovenous malformations (PAVMs) are abnormal dilated vessels which provide a rightto-left (R-L) shunt between the pulmonary arterial and venous circulations.

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Objectives: To assess the occurrence and prognostic factors for the ability to maintain paid work in patients with rheumatoid arthritis (RA). Setting: Inception cohort of patients with RA recruited from rheumatology departments in nine NHS Hospital Trusts in England. Patients: All consecutive patients with RA of less than two years' duration, before any second line (disease modifying) drug treatment, and followed up for five years. Methods: Clinical, laboratory, and radiological assessments, and all treatments were recorded prospectively using a standardised format at presentation and yearly. Outcome measures: Changes in, and loss of paid work by five years' follow up. Results: 732 patients completed the five year follow up. 353/721 (49%) were gainfully employed at the onset of RA, 211 (60%) were still working at five years, 104 (29%) stopped because of the disease, and 31 (9%) retired for reasons other than RA. Work disability at five years was more likely in manual workers (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.4 to 3.8) and worse baseline Health Assessment Questionnaire (HAQ>1.5, OR 2.26, 95% CI 1.38 to 3.7). In combination with other baseline variables (erythrocyte sedimentation rate, sex, age of onset, and radiological erosions), employment outcome was predicted in 78% using multivariate analysis. Conclusions: Nearly half of the patients with RA were in paid employment at onset, work disability was an adverse outcome for a third of these patients by five years, and manual work and high baseline HAQ were important predictors for this. These details are likely to be useful to clinicians, health professionals, and patients in order to plan medical, orthopaedic, and remedial treatments in early RA. Future disease modifying treatments could be compared with this cohort of patients who were treated with conventional second line drugs.

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Purpose: Inhibition of steroid sulfatase (STS), the enzyme responsible for the hydrolysis of steroid sulfates, represents a potential novel treatment for postmenopausal women with hormone-dependent breast cancer. Estrone and DHEA are formed by this sulfatase pathway and can be converted to steroids (estradiol and androstenediol, respectively), which have potent estrogenic properties. Experimental Design: STX64 (667 Coumate), a tricylic coumarin-based sulfamate that irreversibly inhibits STS activity, was selected for entry into the first phase I trial of a STS inhibitor in postmenopausal women with breast cancer. STX64 was administered orally (nine patients at 5 mg and five patients at 20 mg) as an initial dose followed 1week later by 3 Â 2 weekly cycles, with each cycle comprising daily dosing for 5 days followed by 9 days off treatment. Blood and tumor tissue samples were collected for the assessment of STS activity and serum was obtained for steroid hormone measurements before and after treatment. Results: The median inhibition of STS activity by STX64 was 98% in peripheral blood lymphocytes (PBL) and 99% in breast tumor tissue at the end of the 5-day dosing period. As expected, serum concentrations of estrone, estradiol, androstenediol, and DHEA all decreased significantly from pretreatment levels. Unexpectedly, androstenedione and testosterone concentrations also decreased. Four patients, all of whom had previously progressed on aromatase inhibitors, showed evidence of stable disease for 2.75 to 7 months. The drug was well tolerated with only minor drug-related adverse events recorded. Conclusion: STX64 is a potent, well-tolerated STS inhibitor. It inhibits STS activity in PBLs and tumor tissues and causes significant decreases in serum concentrations of steroids with estrogenic properties.

Objectives To assess the spatial and temporal performance of fetal myocardial speckle tracking, using highframe-rate (HFR)

This meta-analysis indicates that children with type 1 diabetes have mild cognitive impairments and subtly reduced overall intellectual functioning.

Objective To assess the possible relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in men, and whether treatment of their ED with sildenafil influences their LUTS. Patients and methods In all, 112 men with ED attending the andrology outpatient clinic were offered oral sildenafil and reviewed 1 and 3 months after treatment. They completed the International Index of Erectile Function and the International Prostate Symptom Score (IPSS) questionnaires at baseline and each review. Scores were designated to indicate the visit number and differences between the visits calculated. Results A third of the men had an initial IPSS of > 7; there was no relationship between baseline urinary and sexual function scores. After treatment with sildenafil, the urinary scores at 3 months correlated strongly with the sexual function scores. There was a significant inverse relationship between the baseline IPSS and sexual function scores after treatment. The overall trend in the IPSS was towards improvement after treatment with sildenafil. Conclusions In men with ED there is no relationship between sexual function scores and urinary symptom scores before treating ED. Treatment with sildenafil appears to improve urinary symptom scores. A lower IPSS at baseline appears to predict a better response to ED therapy with sildenafil.